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De Novo Everolimus-based Therapy for Renal Transplantation Using Rituximab Induction

This study has been terminated.
(Difficulty collecting)
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01312064
First received: January 26, 2011
Last updated: December 26, 2012
Last verified: November 2012
  Purpose

The investigators hypothesized that everolimus-based immunosuppressive therapy combined with rituximab induction could provide comparable safety profiles for renal transplant patients, as compared to standard immunosuppressive therapy using thymoglobulin induction, tacrolimus, mycophenolate mofetil and steroids, in terms of acute rejection rate and renal function.

Rituximab was reported to reverse refractory acute kidney transplant rejection. Combined with immunoadsorption with or without IVIG, rituximab could successfully prevent antibody-mediated rejection in ABO-incompatible renal transplantation. This study is to assess whether a CNI-free regimen including B-cell depleting antibody induction, everolimus and MMF results in comparable long-term function without a negative impact on safety or efficacy of immunosuppression. This study will be open-label and two-arm randomized (2:1).


Condition Intervention Phase
Renal Insufficiency
Drug: rituximab and everolimus
Drug: thymoglobulin and tacrolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Clinical Outcome of de Novo Everolimus-based Immunosuppressive Therapy for Renal Transplantation Using Rituximab Induction

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • acute rejection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The log-rank test will be used to analyse the percentage of rejection-free survival between the two groups. Any patient with a suspicious rejection episode will reveive renal biopsy.


Secondary Outcome Measures:
  • renal function [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Renal function will be estimated by Cockcroft-Gault formula and analysed by 2-tailed student test.

  • adverse event [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    All adverse events and serious adverse events, infections, and malignancies,will be regular monitored including laboratory variables and vital signs and the performance of physical examinations. Number of participants with adverse events will be compared with Chi-square tests.


Enrollment: 2
Study Start Date: April 2011
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: rituximab and everolimus
Patients of the study arm will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation.
Drug: rituximab and everolimus
rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus initial dose: 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation.
Other Name: mabthera
Active Comparator: thymoglobulin and tacrolimus
The control arm will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months.
Drug: thymoglobulin and tacrolimus
thymoglobulin induction and tacrolimus-based immunosuppressive therapy. thymoglobulin dose: 1.0mg/kg/d for 3 days daily dose of tacrolimus: 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation
Other Name: ATG

Detailed Description:

Patients of the study arm (2/3 of the patients) will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation. The control arm (1/3 of the patients) will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months. All patients will receive mycophenolate mofetil (MMF) starting at 2 g/d in divided doses, and then adjusted to maintain WBC between 4000~6000/mm3. All patients entering this study will receive co-trimoxazole as prophylactic medication for at least 12 weeks post-operatively. Valgancyclovir will be given for anti-viral prophylaxis. During the transplant operation, renal biopsy will be performed before vascular perfusion for baseline pathology, and a follow-up biopsy will be scheduled at 2 years after transplantation. The primary endpoint will be incidence of acute rejection, and the secondary endpoints include renal function, graft and patient survival.

Male and female adult patients who are to receive renal transplantation may enter the study. The intention is to enroll 90 patients who have fulfilled inclusion/exclusion criteria into the study. Sixty patients will receive rituximab and everolimus-based therapy, but the other thirty patients will receive thymoglobulin and tacrolimus-based therapy.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients at 15-65 years of age undergoing renal transplantation
  • Patients who have been informed of the potential risks and side effects of the study
  • Patients who have given written informed consent to participate in the study
  • Females who are not pregnant or nursing women (pregnancy test required)

Exclusion Criteria:

  • Donor age greater than 65 years
  • Patients receiving a perfectly matched kidney (6 matches HLA A, B, DR)
  • Patients who are recipients of multiple solid organ transplants
  • Patients undergoing second or subsequent transplantation
  • Patients with pre-transplant PRA > 30%
  • Patients with ABO incompatibility or positive lymphocytotoxicity
  • Patients with severe, active infection
  • Patients who have an abnormal liver profile such as ALT, AST, alkaline phosphatase or total bilirubin >3 times the upper normal limit
  • Patient who are HIV-positive or hepatitis C (PCR+ only) B surface antigen positive
  • Patients who have been treated with an investigational drug or therapy within one month prior to entry or who will be so treated within 6 months of transplantation
  • Patients with a history of malignancy within the last five years except excised squamous or basal cell carcinoma
  • Patients with a history of alcohol or drug abuse or signs of alcohol-induced organ damage, mental dysfunction or other factors limiting their ability to comply fully with the study requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01312064

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: MK Tsai, MD, PhD National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01312064     History of Changes
Other Study ID Numbers: 201011050MB
Study First Received: January 26, 2011
Last Updated: December 26, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
rituximab
everolimus

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Everolimus
Immunosuppressive Agents
Rituximab
Sirolimus
Tacrolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014